Liver and Bile

J Hepatol. 2022;77(2):326–31

Rivero-Juarez A, Frias M, Perez AB, Pineda JA, Reina G, Fuentes-Lopez A, Freyre-Carrillo C, Ramirez-Arellano E, Alados JC, Rivero A; HEPAVIR and GEHEP-014 Study Groups

Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe


Background and aim: Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global.
Methods: Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-immunoglobulin (Ig)M antibodies and/or detectable HEV RNA in serum.
Results: Cohort 1 comprised 169 patients (64.4% male; median age, 43 years) and cohort 2 comprised 98 individuals (68.3% male; median age, 45 years). Of the individuals included in cohort 1, 2 (1.18%; 95% confidence interval [CI]: 0.2–3.8) had detectable Orthohepevirus C RNA in serum. In cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI: 0.06–13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure.

Conclusions: Three cases of Orthohepevirus C were described in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in the study suggests that Orthohepevirus C could be an emerging disease in Europe.

A. Rivero-Juarez, Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain,
E-Mail: arjvet@gmail.com

DOI: 10.1016/j.jhep.2022.01.028

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